Glia- and neuron-specific functions of TrkB signalling during retinal degeneration and regeneration.
Glia- and neuron-specific functions of TrkB signalling during retinal degeneration and regeneration.
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DOI：
10.1038/ncomms1190
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发表时间：
2011-02-08
影响因子：
16.6
通讯作者：
Harada T
中科院分区：
文献类型：
--
作者：
Harada C;Guo X;Namekata K;Kimura A;Nakamura K;Tanaka K;Parada LF;Harada T
神经胶质细胞是中枢神经系统的支持细胞，作为神经细胞存活的介质和神经再生的来源，最近引起了相当大的关注。为了进一步阐明神经胶质细胞和神经细胞在神经变性中的作用，我们培育了 TrkBGFAP 和 TrkBc-kit 敲除小鼠，其中视网膜神经胶质细胞或视网膜内神经元中的 TrkB（脑源性神经营养因子（BDNF）受体）分别被删除。在这里，我们发现这两只突变小鼠中谷氨酸诱导的视网膜变性的程度相似。此外，在 TrkBGFAP 敲除小鼠中，BDNF 不能阻止光感受器变性，也不能刺激 Müller 胶质细胞增殖和退化视网膜中神经标记物的表达。这些结果表明，神经胶质细胞中的 BDNF 信号传导在神经保护和再生中具有重要作用，特别是在穆勒神经胶质细胞向光感受器的转化中。此外，我们的遗传模型提供了一个可以在体内中枢神经系统组织中测试胶质细胞和神经元特异性基因功能的系统。 中枢神经系统含有神经胶质细胞，已被证明在神经元存活中发挥重要作用。原田等人。使用转基因小鼠模型表明，TrkB（生长因子脑源性神经营养因子的受体）是视网膜 Müller 胶质细胞提供神经保护和再生所必需的。
Glia, the support cells of the central nervous system, have recently attracted considerable attention both as mediators of neural cell survival and as sources of neural regeneration. To further elucidate the role of glial and neural cells in neurodegeneration, we generated TrkBGFAP and TrkBc-kit knockout mice in which TrkB, a receptor for brain-derived neurotrophic factor (BDNF), is deleted in retinal glia or inner retinal neurons, respectively. Here, we show that the extent of glutamate-induced retinal degeneration was similar in these two mutant mice. Furthermore in TrkBGFAP knockout mice, BDNF did not prevent photoreceptor degeneration and failed to stimulate Müller glial cell proliferation and expression of neural markers in the degenerating retina. These results demonstrate that BDNF signalling in glia has important roles in neural protection and regeneration, particularly in conversion of Müller glia to photoreceptors. In addition, our genetic models provide a system in which glia- and neuron-specific gene functions can be tested in central nervous system tissues in vivo. The central nervous system contains glial cells, which have been shown to have an important role in neuronal survival. Harada et al. use transgenic mouse models to show that TrkB, a receptor for the growth factor brain-derived neurotrophic factor, is required for retinal Müller glial cells to provide neuroprotection and regeneration.
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